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靶向结直肠癌中ACE2-BRD4的相互作用以及DNA修复和细胞凋亡的失调。

Targeting ACE2-BRD4 crosstalk in colorectal cancer and the deregulation of DNA repair and apoptosis.

作者信息

Zhang Shilan, Kapoor Sabeeta, Tripathi Chakrapani, Perez Jorge Tovar, Mohan Nivedhitha, Dashwood Wan Mohaiza, Zhang Ke, Rajendran Praveen, Dashwood Roderick

机构信息

Center for Epigenetics & Disease Prevention, Texas A&M Health, and Department of Translational Medical Sciences, Texas A&M School of Medicine, Houston, TX, USA.

Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

出版信息

NPJ Precis Oncol. 2023 Feb 18;7(1):20. doi: 10.1038/s41698-023-00361-4.

DOI:10.1038/s41698-023-00361-4
PMID:36801948
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9938505/
Abstract

ACE2 overexpression in colorectal cancer patients might increase susceptibility to SARS-CoV-2 infection. We report that knockdown, forced overexpression, and pharmacologic inhibition in human colon cancer cells targeted ACE2-BRD4 crosstalk to mediate marked changes in DNA damage/repair and apoptosis. In colorectal cancer patients for whom high ACE2 plus high BRD4 expression is predictive of poor survival, pan-BET inhibition would need to consider proviral/antiviral actions of different BET proteins during SARS-CoV-2 infection.

摘要

结直肠癌患者中血管紧张素转换酶2（ACE2）的过表达可能会增加对严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染的易感性。我们报告称，在人结肠癌细胞中进行基因敲低、强制过表达和药理学抑制，可靶向ACE2与含溴结构域蛋白4（BRD4）的相互作用，从而介导DNA损伤/修复和细胞凋亡的显著变化。在高ACE2加上高BRD4表达预示着生存不良的结直肠癌患者中，在SARS-CoV-2感染期间，泛BET抑制需要考虑不同BET蛋白的前病毒/抗病毒作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23da/9938852/7d7ce57cfc73/41698_2023_361_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23da/9938852/eed65b0f2590/41698_2023_361_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23da/9938852/62fb8d82f315/41698_2023_361_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23da/9938852/4d9bbac022e2/41698_2023_361_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23da/9938852/7d7ce57cfc73/41698_2023_361_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23da/9938852/eed65b0f2590/41698_2023_361_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23da/9938852/62fb8d82f315/41698_2023_361_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23da/9938852/4d9bbac022e2/41698_2023_361_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23da/9938852/7d7ce57cfc73/41698_2023_361_Fig4_HTML.jpg

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